Boosting the antitumor effect of doxorubicin by combined correction of hemostasis

Abstract

The size of the primary tumor and number of metastases to the lungs in mice with Lewis pulmonary carcinoma treated with doxorubicin were, respectively, 3 and 2.2 times less than in the control. Injection of doxorubicin and heparin led to an 8-fold reduction of the tumor. The number of animals with detected metastases to the lungs and the mean number of metastases per animal were decreased. Supplementation of doxorubicin therapy with a complex of drugs correcting platelet aggregation and the antithrombogenic properties of the vascular wall resulted in a reduction of the number of metastases on the lung surface in comparison with the control and with the animals treated with doxorubicin alone. Key Words: vascular platelet hemostasis; doxorubicin; metastasesThe adhesion of tumor cells to blood vessel walls, the formation of an oncogenic-thrombogenic embolus and its entrapment in the microcirculatory bed, followed by the development of metastases depend to a great extent on the antithrombogenic activity of the vascular wall and the characteristics of platelet aggregation [6,9]. The antiaggregation and anticoagulation activity of the wall was previously shown to decline during experimental malignant cell growth, whereas the functional activity of platelets increased [4]. A reduction of the antithrombogenic properties of the vascular wall, namely depressed synthesis and release of prostacycline, antithrombin III, and plasminogen activator into the blood in cancer patients, was revealed in an earlier study [1].We investigated the relationship between the modification of the function of the hemostasis sys-